Human and mouse CD137 have predominantly different binding CRDs to their respective ligands

Ling Yi; Yanlin Zhao; Xiaojue Wang; Min Dai; Karl Erik Hellström; Ingegerd Hellström; Hongtao Zhang

doi:10.1371/journal.pone.0086337

Human and mouse CD137 have predominantly different binding CRDs to their respective ligands

PLoS One. 2014 Jan 21;9(1):e86337. doi: 10.1371/journal.pone.0086337. eCollection 2014.

Authors

Ling Yi¹, Yanlin Zhao², Xiaojue Wang¹, Min Dai³, Karl Erik Hellström³, Ingegerd Hellström³, Hongtao Zhang¹

Affiliations

¹ Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
² Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
³ Department of Pathology, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America.

Abstract

Monoclonal antibodies (mAbs) to CD137 (a.k.a. 4-1BB) have anti-tumor efficacy in several animal models and have entered clinical trials in patients with advanced cancer. Importantly, anti-CD137 mAbs can also ameliorate autoimmunity in preclinical models. As an approach to better understand the action of agonistic and antagonistic anti-CD137 mAbs we have mapped the binding region of the CD137 ligand (CD137L) to human and mouse CD137. By investigating the binding of CD137L to cysteine rich domain II (CRDII )and CRDIII of CD137, we found that the binding interface was limited and differed between the two species in that mouse CD137L mainly combined with CRDII and human CD137L mainly combined with CRDIII.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-1BB Ligand / metabolism*
Animals
Antibodies, Monoclonal / metabolism
COS Cells
Chlorocebus aethiops
Cysteine / metabolism*
Humans
Leukocytes, Mononuclear / metabolism
Mice
Protein Binding / physiology
Recombinant Fusion Proteins / metabolism
Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*

Substances

4-1BB Ligand
Antibodies, Monoclonal
Recombinant Fusion Proteins
Tumor Necrosis Factor Receptor Superfamily, Member 9
Cysteine

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81273209 and 30572123), National Basic Research Program of China (the “973” Program, No. 2014CB744403), Beijing Science and Technology Foundation of China (grant number Z121107001012146), and supported in part by National 12.5 grant (2013ZX10003003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.